The major aim of this work is to provide a quantitative description of the gelation of hemoglobin S that can be used for understanding the pathophysiology of sickle cell disease and the development of therapeutic agents. The delay time of hemoglobin S gelation plays a critical role in the pathophysiology of sickle cell disease. At physiological saturations with oxygen gelation takes place in the majority of sickle cells at equilibrium in vitro, but is prevented from occurring in vivo because the delay times are sufficiently long that most cells return to the lungs and are reoxygenated before gelation has begun. To extend this description a laser photolysis technique is being developed to measure the delay time as a function of saturation on physiological time scales over a wide range of hemoglobin S concentrations and saturations. With these data it will be possible to provide a more complete description of gelation in vivo. The measurement of the delay time on single cells using the laser photolysis technique can also be used as a sensitive method to assess the potential efficacy of agents that are potential drugs for the treatment of sickle cell disease. Once this technique is automated, it will be possible to examine a large number of agents, to compare intracellular gelation and clinical severity, and to follow changes in intracellular gelation in patients on various therapeutic protocols.